Changes in the radiological depth correlate with dosimetric deterioration in particle therapy for stage I NSCLC patients under high frequency jet ventilation.

BACKGROUND: Particle dose distributions are highly sensitive to anatomy changes in the beam path, which may lead to substantial dosimetric deviations. Robust planning and dedicated image guidance together with strategies for online decision making to counteract dosimetric deterioration are thus mandatory. We aimed to develop methods to quantify anatomical discrepancies as depicted by repeated computed tomography (CT) imaging and to test whether they can predict deviations in target coverage. MATERIAL AND METHODS: Dedicated software tools allowed for voxel-based calculations of changes in the water equivalent path length (WEPL) in beam directions. We prepared proton and carbon ion plans with different coplanar beam angle settings on a series of lung cancer patients, for which planning and localization CT scans under high frequency jet ventilation (HFJV) for tumor fixation were performed. We investigated the reproducibility of target coverage between the optimized and recalculated treatment plans. We then studied how different raster scan and planning settings influence the robustness. Finally, we carried out a systematic analysis of the variations in the WEPL along different coplanar beam angles to find beam directions, which could minimize such variations. RESULTS: The Spearman's correlations for the GTV ΔV95 and ΔV98 with the ΔWEPL for the proton plans with a 0° and -45° two-field configuration were 0.701 (p = 0.02) and 0.719 (p = 0.08), respectively. For beam configurations 0° and -90°, or 0° and + 45°, with lower ΔWEPL, the correlations were no significant. The same trends were observed for the carbon ion plans. Increased beam spot overlap reduced dosimetric deterioration in case of large ΔWEPL. CONCLUSION: Software tools for fast online analysis of WEPL changes might help supporting clinical decision making of image guidance. Raster scan and treatment planning settings can help to compensate for anatomical deviations.

Reproducibility of target coverage in stereotactic spot scanning proton lung irradiation under high frequency jet ventilation.

PURPOSE: To investigate scanned-beam proton dose distribution reproducibility in the lung under high frequency jet ventilation (HFJV). MATERIALS AND METHODS: For 11 patients (12 lesions), treated with single-fraction photon stereotactic radiosurgery under HFJV, scanned-beam proton plans were prepared with the TRiP98 treatment planning system using 2, 3-4 and 5-7 beams. The planning objective was to deliver at least 95% of the prescription of 33 Gy (RBE) to 98% of the PTV. Plans were subsequently recomputed on localization CT scans. Additionally, for selected cases, the effects of range uncertainties were investigated. RESULTS: Median GTV V(98%) was 98.7% in the original 2-field plans and 93.7% in their recomputation (p=0.039). The respective values were 99.0% and 98.0% (p=0.039) for the 3-4-field plans and 100.0% and 99.6% (p=0.125) for the 5-7-field plans. CT calibration uncertainties of ±3.5% led to a GTV V(98%) reduction below 1.5 percentual points in most cases and reaching 3 percentual points for 2-field plans with beam undershoot. CONCLUSIONS: Through jet ventilation, reproducible tumor fixation for proton radiotherapy of lung lesions is achievable, ensuring excellent target coverage in most cases. In few cases, non-optimal patient setup reproducibility induced density changes across beam entrance channels, leading to dosimetric deterioration between planning and delivery.

Stereotactic, single-dose irradiation of lung tumors: a comparison of absolute dose and dose distribution between pencil beam and Monte Carlo algorithms based on actual patient CT scans.

PURPOSE: Dose calculation based on pencil beam (PB) algorithms has its shortcomings predicting dose in tissue heterogeneities. The aim of this study was to compare dose distributions of clinically applied non-intensity-modulated radiotherapy 15-MV plans for stereotactic body radiotherapy between voxel Monte Carlo (XVMC) calculation and PB calculation for lung lesions. METHODS AND MATERIALS: To validate XVMC, one treatment plan was verified in an inhomogeneous thorax phantom with EDR2 film (Eastman Kodak, Rochester, NY). Both measured and calculated (PB and XVMC) dose distributions were compared regarding profiles and isodoses. Then, 35 lung plans originally created for clinical treatment by PB calculation with the Eclipse planning system (Varian Medical Systems, Palo Alto, CA) were recalculated by XVMC (investigational implementation in PrecisePLAN [Elekta AB, Stockholm, Sweden]). Clinically relevant dose-volume parameters for target and lung tissue were compared and analyzed statistically. RESULTS: The XVMC calculation agreed well with film measurements (<1% difference in lateral profile), whereas the deviation between PB calculation and film measurements was up to +15%. On analysis of 35 clinical cases, the mean dose, minimal dose and coverage dose value for 95% volume of gross tumor volume were 1.14 ± 1.72 Gy, 1.68 ± 1.47 Gy, and 1.24 ± 1.04 Gy lower by XVMC compared with PB, respectively (prescription dose, 30 Gy). The volume covered by the 9 Gy isodose of lung was 2.73% ± 3.12% higher when calculated by XVMC compared with PB. The largest differences were observed for small lesions circumferentially encompassed by lung tissue. CONCLUSIONS: Pencil beam dose calculation overestimates dose to the tumor and underestimates lung volumes exposed to a given dose consistently for 15-MV photons. The degree of difference between XVMC and PB is tumor size and location dependent. Therefore XVMC calculation is helpful to further optimize treatment planning.

High-frequency jet ventilation for complete target immobilization and reduction of planning target volume in stereotactic high single-dose irradiation of stage I non-small cell lung cancer and lung metastases.

PURPOSE: To demonstrate the feasibility of complete target immobilization by means of high-frequency jet ventilation (HFJV); and to show that the saving of planning target volume (PTV) on the stereotactic body radiation therapy (SBRT) under HFJV, compared with SBRT with respiratory motion, can be predicted with reliable accuracy by computed tomography (CT) scans at peak inspiration phase. METHODS AND MATERIALS: A comparison regarding different methods for defining the PTV was carried out in 22 patients with tumors that clearly moved with respiration. A movement span of the gross tumor volume (GTV) was defined by fusing respiration-correlated CT scans. The PTV enclosed the GTV positions with a safety margin throughout the breathing cycle. To create a PTV from CT scans acquired under HFJV, the same margins were drawn around the immobilized target. In addition, peak inspiration phase CT images (PIP-CTs) were used to approximate a target immobilized by HFJV. RESULTS: The resulting HFJV-PTVs were between 11.6% and 45.4% smaller than the baseline values calculated as respiration-correlated CT-PTVs (median volume reduction, 25.4%). Tentative planning by means of PIP-CT PTVs predicted that in 19 of 22 patients, use of HFJV would lead to a reduction in volume of >or=20%. Using this threshold yielded a positive predictive value of 0.89, as well as a sensitivity of 0.94 and a specificity of 0.5. CONCLUSIONS: In all patients, SBRT under HFJV provided a reliable immobilization of the GTVs and achieved a reduction in PTVs, regardless of patient compliance. Tentative planning facilitated the selection of patients who could better undergo radiation in respiratory standstill, both with greater accuracy and lung protection.

Stereotactic, high single-dose irradiation of stage I non-small cell lung cancer (NSCLC) using four-dimensional CT scans for treatment planning.

We reviewed response rates, local control, survival and side effects after non-fractionated stereotactic high single-dose body radiation therapy for lung tumors. Forty patients with stage I non-small cell lung cancer (NSCLC) underwent radiosurgery involving single-dose irradiation. The standard dose prescribed to the isocenter was 30Gy with an axial safety margin of 10mm and a longitudinal safety margin of 15mm. The planning target volume (PTV) was defined using three CT scans with reference to the phases of respiration so that the movement span of the clinical target volume (CTV) was enclosed. The volume of the bronchial carcinomas varied from 4.2 to 130cm(3) (median: 19.5cm(3)), and the PTV derived from four-dimensional CT (4D-CT) scans using image fusion ranged from 15.6 to 390.5cm(3) (median: 101cm(3)). Tumor size ranged from 1.7 to 10cm at largest focuses. Follow-up periods varied from 6.0 to 61.5 months (median: 20 months). We observed three local tumor recurrences, resulting in an actuarial local tumor control of 81% at 3 years. With the exception of two rib fractures, no serious late toxicity was observed. The overall survival probability rates were: 2 years: 66%, 3 years: 53% (median overall survival: 37 months). Cancer-specific survival probability was: 2 years: 71%, 3 years: 57%. Non-fractionated high single-dose SBRT for NSCLC is more convenient for the patient and less time-consuming than hypofractionated SBRT, but data dealing with this method are still scanty. This alternative treatment results in favourable local control and acceptable toxicity.

Stereotactic, single-dose irradiation of stage I non-small cell lung cancer and lung metastases.

BACKGROUND: We prospectively reviewed response rates, local control, and side effects after non-fractionated stereotactic high single-dose body radiation therapy for lung tumors. METHODS: Fifty-eight patients underwent radiosurgery involving single-dose irradiation. With 25 patients, 31 metastases in the lungs were irradiated; with each of 33 patients, stage I non-small cell lung cancer (NSCLC) was subject to irradiation. The standard dose prescribed to the isocenter was 30 Gy with an axial safety margin of 10 mm and a longitudinal safety margin of 15 mm. The planning target volume (PTV) was defined using three CT scans with reference to the phases of respiration so that the movement span of the clinical target volume (CTV) was enclosed. RESULTS: The volume of the metastases (CTV) varied from 2.8 to 55.8 cm3 (median: 6.0 cm3) and the PTV varied from 12.2 to 184.0 cm3 (median: 45.0 cm3). The metastases ranged from 0.7 to 4.5 cm in largest diameter. The volume of the bronchial carcinomas varied from 4.2 to 125.4 cm3 (median: 17.5 cm3) and the PTV from 15.6 to 387.3 cm3 (median: 99.8 cm3). The bronchial carcinomas ranged from 1.7 to 10 cm in largest diameter. Follow-up periods varied from 6.8 to 63 months (median: 22 months for metastases and 18 months for NSCLC). Local control was achieved with 94% of NSCLC and 87% of metastases. No serious symptomatic side effects were observed. According to the Kaplan-Meier method the overall survival probability rates of patients with lung metastases were as follows: 1 year: 97%, 2 years: 73%, 3 years: 42%, 4 years: 42%, 5 years: 42% (median survival: 26 months); of those with NSCLC: 1 year: 83%, 2 years: 63%, 3 years: 53%, 4 years: 39%: (median survival: 20.4 months). CONCLUSION: Non-fractionated single-dose irradiation of metastases in the lungs or of small, peripheral bronchial carcinomas is an effective and safe form of local treatment and might become a viable alternative to invasive techniques.

Neuroelectric source imaging of steady-state movement-related cortical potentials in human upper extremity amputees with and without phantom limb pain.

Whereas several studies reported a close relationship between changes in the somatotopic organization of primary somatosensory cortex and phantom limb pain, the relationship between alterations in the motor cortex and amputation-related phenomena has not yet been explored in detail. This study used steady-state movement-related cortical potentials (MRCPs) combined with neuroelectric source imaging to assess the relationship of changes in motor cortex and amputation-related phenomena such as painful and non-painful phantom and residual limb sensations, telescoping, and prosthesis use. Eight upper limb amputees were investigated. A significant positive relationship between reorganization of the motor cortex (distance of the MRCP source location from the mirrored source for hand movement) and phantom limb pain was found. Non-painful phantom sensations as well as painful and non-painful residual limb sensations were unrelated to motor cortical reorganization. A higher amount of motor reorganization was associated with less daily prosthesis use, which also tended to be related to more severe phantom limb pain. These results extend previous findings of a positive relationship between somatosensory reorganization and phantom limb pain to the motor domain and suggest a potential positive effect of prosthesis use on phantom limb pain and cortical reorganization.

Reproducibility and stability of neuroelectric source imaging in primary somatosensory cortex.

The present study investigated the test-retest reliability of EEG source localization of somatosensory evoked potentials (SEPs) over an extended time period and tested the accuracy of source reconstruction co-registred with individual brain morphology (MRIs). Seven healthy subjects were stimulated pneumatically at the first digit and fifth digit of each hand and at the left and right lower corner of the mouth in two sessions spaced several weeks apart. At each location 1000 stimuli were presented. The overlay of the dipole localizations with the individual anatomic structure of the subjects' cortex was accomplished by the use of magnetic resonance images. A spherical 4-shell model of the head was used to localize the neuroelectric sources of the EEG data. In two cases a more realistically shaped 3 compartment model was computed using the boundary element method (BEM). The source localizations of the SEP component were found to be highly reproducible: the mean standard deviation of the dipole locations was 5.21 mm in the x-, 5.98 mm in the y- and 4.22 mm in the z-direction. BEM was not found to be superior to a 4-shell model. These data support the use of multi-electrode EEG recordings combined with MRI as an adequate method for the investigation of the functional organization of the somatosensory cortex.

Reliability and validity of neuroelectric source imaging in primary somatosensory cortex of human upper limb amputees.

The present study investigated the test-retest reliability of EEG source localizations of somatosensory evoked potentials (SEPs) in human upper limb amputees over a long time frame (several months) and examined the validity of source reconstruction. In two sessions spaced several months apart five unilateral upper limb amputees were stimulated at the first and fifth digit of the intact hand and at the left and right lower corner of the mouth. To examine the validity of the results of the neuroelectric source reconstruction a comparison with neuromagnetic source localization was performed for two subjects. The source localizations of the SEP components were found to be highly reproducible: the mean standard deviation of the dipole locations was 8.80 mm in the x-, 7.00 mm in the y- and 4.15 mm in the z-direction. The match of the comparison of EEG and MEG data was in the range of one centimeter. These results support the use of multi-electrode EEG recordings combined with MRI as an adequate method for the investigation of the functional organization of the somatosensory cortex in upper limb amputees and suggest high stability of cortical reorganization in these subjects.